Given how little is known about the wider effects of antidepressants, we wanted to understand more about how these drugs affect the cells in our brains and bodies. What we found was that most antidepressants regulate the same key biological process across many tissues, which likely has little to do with their effect on depression. Furthermore, our data suggests that a single antidepressant dose may be enough to effectively open up the blood-brain barrier for delivery of other drugs. We hope that this finding may help improve clinical efficacy and drive down the treatment cost for new drugs against dementia, which currently are unavailable to millions of people who need them. Besides that, we are excited to explore whether antidepressants may help deliver drugs into other hard-to-reach corners of the body.
Dr Oleg Glebov, King's IoPPN
31 May 2024
New research finds antidepressants may help deliver other drugs into the brain
Study finds that antidepressants control the permeability of cells in the blood-brain barrier, showing potential to improve the efficacy of drugs against Alzheimer’s disease and other brain disorders.
Since the 1980s, selective serotonin reuptake inhibitor (SSRI) antidepressants have been the backbone of treatment for depression and other mental health conditions worldwide, with tens of millions of annual prescriptions in the UK alone. Yet their mechanisms of action - and their wider effects across the body – are still not fully understood. Now, a study led by King’s researchers has been published in Molecular Psychiatry, identifying a key biological process targeted by SSRIs and proposing the use of these drugs in new clinical applications.
In this work, all currently prescribed SSRIs were tested on various types of cells grown in Petri dishes, using similar drug concentrations to those found in blood of patients treated for depression. Unexpectedly, almost all antidepressants affected the ability of cells to transport material in and out of their environment through a process called membrane trafficking. Moreover, a single injection of an antidepressant fluvoxamine in mice enabled a fluorescent compound that would normally stay outside the brain to accumulate inside the brain, crossing the cell barrier separating the brain from the rest of the body.
Exactly how SSRIs control membrane trafficking remains unclear, and finding out the molecular-level intricacies will require collaboration across multiple scientific disciplines. Likewise, whether SSRIs are actually any good for delivering other drugs in humans will need to be determined in the clinic. Nevertheless, it is entirely possible that this study can signal the start of a brand new career for these venerable 30+ year-old drugs - this time, helping other drugs do their job.
Du, W., Chen, H., Gróf, I. et al. Antidepressant-induced membrane trafficking regulates blood-brain barrier permeability. Mol Psychiatry (2024). https://doi.org/10.1038/s41380-024-02626-1
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Lecturer in Old Age Psychiatry